A Network of Genetic Effects on Non-Demented Cognitive Aging: Alzheimer's Genetic Risk (CLU + CR1â+âPICALM) Intensifies Cognitive Aging Genetic Risk (COMT + BDNF) Selectively for APOEÉ4 Carriers.
J Alzheimers Dis
; 62(2): 887-900, 2018.
Article
em En
| MEDLINE
| ID: mdl-29480189
ABSTRACT
BACKGROUND:
Trajectories of complex neurocognitive phenotypes in preclinical aging may be produced differentially through selective and interactive combinations of genetic risk.OBJECTIVE:
We organize three possible combinations into a "network" of genetic risk indices derived from polymorphisms associated with normal and impaired cognitive aging, as well as Alzheimer's disease (AD). Specifically, we assemble and examine three genetic clusters relevant to non-demented cognitive trajectories 1) Apolipoprotein E (APOE), 2) a Cognitive Aging Genetic Risk Score (CA-GRS; Catechol-O-methyltransferase + Brain-derived neurotrophic factor), and 3) an AD-Genetic Risk Score (AD-GRS; Clusterin + Complement receptor 1â+âPhosphatidylinositol-binding clathrin assembly protein).METHOD:
We use an accelerated longitudinal design (nâ=â634; age rangeâ=â55-95 years) to test whether AD-GRS (low versus high) moderates the effect of increasing CA-GRS risk on executive function (EF) performance and change as stratified by APOE status (É4+ versus É4-).RESULTS:
APOEÉ4 carriers with high AD-GRS had poorer EF performance at the centering age (75 years) and steeper 9-year decline with increasing CA-GRS but this association was not present in APOEÉ4 carriers with low AD-GRS.CONCLUSIONS:
APOEÉ4 carriers with high AD-GRS are at elevated risk of cognitive decline when they also possess higher CA-GRS risk. Genetic risk from both common cognitive aging and AD-related indices may interact in intensification networks to differentially predict (1) level and trajectories of EF decline and (2) potential selective vulnerability for transitions into impairment and dementia.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Apolipoproteína E4
/
Doença de Alzheimer
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Disfunção Cognitiva
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Envelhecimento Cognitivo
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article